The neurological mutants of mice provide a powerful technique for dissecting the complex events involved in the development of the mammalian central nervous system. This proposal concentrates on the development of a single structure, the cortex of the cerebellum. A series of mutants: staggerer, Lurcher, leaner and tottering will be used. Much as several bacterial mutants affecting a single biochemical pathway aid in the elucidation of the reactions involved, several neurological mutants affecting the same structure should aid in the identification of the forces at work during cerebellar development. The first area of study will be a quantitative morphological approach. A numerical picture coupled with the conventional cytology provides a fresh perspective and often leads to findings missed in previous studies (for example the absence of 75% of the medium-to-large neurons in the cerebellar cortex of staggerer mice and the depletion of this same neuronal category in the lateral cerebellum of the "unaffected" staggerer heterozygote). The second area of study will be the examination of mutant yields wild-type chimeras. These unusual animals greatly enhance the power of the genetics by allowing the experimenter to view the interaction of genotypically wild-type and mutant cells in a single mouse. In so doing, they remove from the study such variables as different internal physiology and slightly different developmental timing. Thus, they aid tremendously in separating genetic from epigenetic events. Finally, some recent exciting experiments with microbial carbohydrate-specific antibodies and with plant lectins have shown that wild-type cerebellar granule cells undergo a change in the carbohydrate characteristics of their cell surface between the first and seventh postnatal day. When staggerer granule cells were examined they were found to retain their "embryonic" surface. This preliminary work will be pursued in staggerer as well as the other mutants and in the chimeric studies. If successful, the results may serve to bridge the gap between the molecular of the genetic lesion and the descriptive neuropathology that currently defines the neurological mutants.